Current status and future prospects of toxicity assessment using organoids.

Abstract

Organoids offer innovative platforms for toxicity assessment by more accurately recapitulating the structural and functional complexity of human tissues compared to traditional 2D cultures and animal models. This review summarizes current applications and discusses future directions for kidney, cardiac, liver, and brain organoids within the context of toxicology. Brain organoids, which recapitulate key features of human neural development, have facilitated investigations into neurotoxicity induced by agents such as Zika virus and chlorpyrifos. Kidney organoids, with nephron-like structures, have been employed to model nephrotoxicity induced by chemotherapeutic agents. Cardiac organoids, which mimic heart contractions and electrical properties, are effective for assessing cardiotoxicity from drugs such as doxorubicin. Liver organoids allow prediction of hepatotoxicity through the modeling of human-specific drug metabolism, as shown in studies using compounds like acetaminophen and troglitazone. Despite their promise, organoid systems still face challenges such as cellular immaturity, batch-to-batch variability, and limited vascularization. Emerging technologies such as 3D bioprinting, vascular integration, and multi-organ assembly are expected to improve the applicability of organoids in toxicity testing. Additionally, integration with microfluidic platforms and artificial intelligence-based analysis will improve high-throughput screening and predictive accuracy. As these technologies continue to evolve, organoids are poised to play a critical role in safer drug development, reducing dependence on animal models and providing deeper insights into systemic toxicity.